| Background and ObjectiveEpithelial ovarian cancer(ovarian cancer) is one of the three kinds of malignant tumor in female genital organs, the disease incidence ranks the third second only to cervical cancer and endometrial cancer and it gradually raises tendency around the world. Because of the particularity of its biological behavior, it is prone to happening multiple ways and multiple sites of metastasis in early stage, ovarian cancer patients of 70% found were already late, five-year survival rate is still hovering around 30%. In the last 20 years, although the surgery, chemotherapy and other treatments of ovarian cancer have further improved, but due to the characteristics of malignant tumors'invasive growth, their mortality rates are the leading of gynecologic malignant tumors. Therefore, looking for the objective reference index and effective treatment method of the predicted ovarian cancer invasion and metastasis are currently the hot spots of ovarian cancer research.Tight junctions are on top of the junction complex of epithelial cells and endothelial cells. It not only has the functions of cell adhesion, maintaining cell polarity and permeability, in addition, it can help signal molecular transfer protein, regulate cell proliferation and differentiation and so on. Tight junctions play an important role in epithelial cells and endothelial cells. Tight junctions mainly include tight junction adhesion molecules, Occludins, Claudins and so on transmembrane proteins, however, Claudins are the skeleton proteins of the tight junctions. Up to now, the exact roles of Claudins remain unclear, the homogeneous or heterogeneous Claudins may be form polymers, and the interactions with the neighboring Claudins constitute the skeleton of intercellular connections. The cell differentiation of normal tissue is highly ordered, but the tumor tissue is usually a lack of this feature, and the latter is poorly differentiated, disappeared in intercellular polarity and tight junction dysfunction. At present the view that the destruction of the integrity of tight junctions may be one of the reasons of leading to tumor cell migration and diffusion of nutritional factors needed for growth. Thus, the abnormal expression of Claudins led to the abnormalities of tight junction structure and function, which led to the occurrence, development and transfer of cancer.By detecting the expressions of Claudin-3 and Claudin-4 proteins in epithelial ovarian cancer tissue, we analysed the relationship between their expression in epithelial ovarian cancer and clinicopathological features respectively and their correlation, and reavealed their roles in occurrence and development, invasion and metastasis of epithelial ovarian cancer, in order to provide theory basis for the clinical treatments of epithelial ovarian cancer.Materials and Methods1 One hundred and two cases were taken from the file organization of the patients for surgical specimens which were from the department of pathology, the First Affiliated Hospital of Zhengzhou University from January 2006 to October 2008. 10 cases of normal ovarian tissues (normal group) were as control,which were from operation for uterine myoma and at the same time were taken ovarian tissues for ovarian biopsy; 15 cases of benign epithelial ovarian tumor tissues (benign groups), which include 11 cases of serous cystadenoma,4 cases of mucinous cystadenoma; 12 cases of borderline epithelial ovarian tumor tissues(borderline groups), which include 9 cases of borderline serous cystadenoma,3 cases of borderline mucinous cystadenoma; 65 cases of epithelial ovarian cancer tissues(ovarian cancer groups), which include 34 cases of serous adenocarcinoma,15 cases of mucinous cystadenocarcinoma,14 cases of endometrial carcinoma and 2 cases of clear cell carcinoma. They were all initial cases. All the patients didn t have any radiotherapy, chemotherapy and other therapy before operation. The patients'age was 18 to 74 years, median age was 52 years, and there was not significant difference between groups (P> 0.05).2 Using immunohistochemistry method to detect the expressions of Claudin-3 and Claudin-4 proteins in above-mentioned tissues, to analyse the relationship between their expression and clinicalpathological features in epithelial ovarian cancer respectively and their correlation, and reveal their roles in occurrence and development, invasion and metastasis of epithelial ovarian cancer.3 SPSS13.0 statistical software was used for data processing, count data were analyzed by Chi-Square Tests and Fisher Exact Test, and the relationships of the two used Spearman rank correlation. To a=0.05 as the level of statistical significance tests.Results1 The expression of Claudin-3 was negative in normal groups. The positive expression rate of Claudin-3 in benign groups, borderline groups and ovarian cancer groups was 26.7%,50.0%,81.5% respectively, there were significantly differences among the four groups (χ2=35.443, P=0.000). However, the expression of Claudin-3 in ovarian cancer groups was significantly higher than in normal groups, benign groups and borderline groups(P<0.05), the expression of Claudin-3 in borderline groups was significantly higher than in normal groups(P<0.05); The positive expression rate of Claudin-4 in normal groups, benign groups, borderline groups and ovarian cancers groups was 10%,20%,66.7%,86.2% respectively, there were significantly differences among the four groups (χ2=40.258, P=0.000). However, the expression of Claudin-4 in ovarian cancer groups and borderline groups were significantly higher than those in benigngroups and normal groups, there were statistical significances between them(P<0.05).2 The positive expression rate of Claudin-3 and Claudin-4 showed no statistical differences between different ages, histological type, clinical stage(P>0.05).3 The positive expression rate of Claudin-3 in high grade differentiated, medium grade differentiated, and low grade differentiated epithelial ovarian cancers was 50.0 %,89.7% and 95.0% respectively, there was statistical significance among them(χ2 =14.249, P=0.001), but there was statistical significance between high grade differentiated and medium grade differentiated(P<0.05); The positive expression rate of Claudin-4 in high grade differentiated,medium grade differentiated, and low grade differentiated epithelial ovarian cancers was 62.5%,93.1%和95.0%, there was statistical significance among them(χ2=9.991,P=0.007), but the expression of Claudin-4 in medium grade differentiated and low grade differentiated were significantly higher than that in high grade differentiated(P<0.05);The positive expression rate of Claudin-3 Claudin-4and in epithelial ovarian cancers with lymph node metastasis was significantly higher than those without lymph node metastasis, there were statistical significance between them(respectively:χ2=4.710, P=0.030;χ2 =4.065,P=0.044).4 Positive expression of Claudin-3 was observed in 53 epithelial ovarian cancers, negative expression of Claudin-3 was observed in 12 epithelial ovarian cancers; Positive expression of Claudin-4 was observed in 56 epithelial ovarian cancers, negative expression of Claudin-3 was observed in 9 epithelial ovarian cancers. Spearman correlation coefficients show significant positive correlation between the expression of Claudin-3 and Claudin-4(r=0.588, P=0.000).Conclusions1 With the increase in malignant ovarian tissue, the expression level of Claudin-3 and Claudin-4 gradually increased, and the expression of the two in ovarian cancer was positively correlated, which indicated that the two may co-promote the occurrence, development of ovarian cancer.2 The expressions of Claudin-3 and Claudin-4 related with cell differentiation, and the expression of them with lymph node metastasis were significantly higher than without lymph node metastasis, which indicated that Claudin-3 and Claudin-4 can be used as the index in estimating the invasion and metastasis of epithelial ovarian cancer.
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